The following description of the background of the invention is provided to aid in understanding the invention, but is not admitted to describe or constitute prior art to the invention. The contents of the articles, patents, and patent applications, and all other documents and electronically available information mentioned or cited in this application, are hereby incorporated by reference in their entirety to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. Applicants reserve the right to physically incorporate into this application any and all materials and information from any such articles, patents, patent applications, or other documents.
Pancreatic adenocarcinoma has a five-year survival rate of only 5%, making it the fourth-leading cause of cancer death in the United States. “Cancer Statistics 2008,” (website: cancer.org). Current diagnostic procedures are unable to diagnose the disease in its early stages. T. P. Yeo, et al., “Pancreatic cancer,” Current Problems in Cancer 26, 176-275 (2002). In addition, diagnosis is compromised due to an overlap of symptoms with pancreatitis (inflammation of the pancreas). As a result, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), an established method for the diagnosis of pancreatic adenocarcinoma, has only 54% sensitivity for cancer in the setting of pancreatitis. A. Fritscher-Ravens et al., “Endoscopic ultrasound-guided fine-needle aspiration in focal pancreatic lesions: a prospective intraindividual comparison of two needle assemblies,” Endoscopy 33, 484-490 (2001). As many as 9% of patients undergo complicated Whipple surgery to remove a significant portion of their pancreas, only to reveal absence of the disease during pathological examination of the resected specimen. S. C. Abraham et al., “Pancreaticoduodenectomy (Whipple Resections) in Patients Without Malignancy: Are They All ‘Chronic Pancreatitis’?,” The American Journal of Surgical Pathology 27, 110-120 (2003).
Clearly, the detection of the disease in its early stages and its distinction from pancreatitis would greatly reduce the instances of unnecessary surgery, and more importantly, improve the chances of patient survival.
Multiple studies over the years have employed optical techniques as a means for minimally invasive detection of breast, cervical, colon, and esophageal cancer, among other things. Z. Volynskaya et al., “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J Biomed Opt 13, 024012 (2008); G. Zonios et al., “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Applied Optics 38, 6628-6637 (1999); S. K. Chang et al., “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J Biomed Opt 11,—(2006); and I. Georgakoudi and M. S. Feld, “The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett's esophagus,” Gastrointestinal Endoscopy Clinics of North America 14, 519-537 (2004).
However, there is little support for applying optical methods for pancreatic cancer detection, possibly owing to the relatively inaccessibility of the pancreas.
Recently, it is understood that Optical Coherence Tomography (OCT) has been applied to both in vivo and ex vivo detection of pancreatic cancer. P. A. Testoni et al., “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am J Gastroenterol 102, 269-274 (2007); P. A. Testoni et al., “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an Ex Vivo study,” Am J Gastroenterol 100, 2777-2783 (2005).
Furthermore, Near-Infrared Spectroscopy and Partial-wave microscopic spectroscopy have also been applied in ex vivo studies. V. R. Kondepati et al., “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J Biomed Opt 10,—(2005); H. Subramanian et al., “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt Lett 34, 518-520 (2009). In the latter, pancreatic cancer cells on microscopic slides were studied. Four-dimensional elastic light-scattering spectroscopy, and low-coherence enhanced backscattering spectroscopy have been employed for the ex vivo study of duodenal tissue based on a field effect hypothesis that predicts changes in the duodenum owing to the presence of cancer in the pancreas. V. Turzhitsky et al., “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis Markers 25, 313-321 (2008); Y. Liu et al., “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin Cancer Res 13, 4392-4399 (2007).
A number of chemometric and statistical techniques have been used in the literature to develop tissue classification algorithms employing optical spectroscopy data. These include, multiple linear regression analysis, linear discriminant analysis, backpropagating neural network analysis, principal component analysis, logistic discrimination, partial least squares, multivariate linear regression, and support vector machine. N. Ramanujam et al., “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers in Surgery and Medicine 19, 46-62 (1996); Z. F. Ge et al., “Identification of colonic dysplasia and neoplasia by diffuse reflectance spectroscopy and pattern recognition techniques,” Applied Spectroscopy 52, 833-839 (1998); G. M. Palmer et al., “Comparison of Multiexcitation Fluroescence and Diffuse Reflectance Spectroscopy for the Diagnosis of Breast Cancer,” Ieee T Bio-Med Eng 50, 1233-1242 (2003); S. K. Chang et al., “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer,” J Biomed Opt 10, 024031 (2005); A. Dhar et al., “Elastic scattering spectroscopy for the diagnosis of colonic lesions: initial results of a novel optical biopsy technique,” Gastrointest Endosc 63, 257-261 (2006); S. C. Chu et al., “Comparison of the performance of linear multivariate analysis methods for normal and dyplasia tissues differentiation using autofluorescence spectroscopy,” Ieee T Bio-Med Eng 53, 2265-2273 (2006); and G. Salomon et al., “The Feasibility of Prostate Cancer Detection by Triple Spectroscopy,” Eur Urol, (2008). Additionally, quantitative photon-tissue interaction models of reflectance and fluorescence have been utilized in optical methods for detecting breast cancer [4], colon cancer [5], cervical cancer [6], and Barrett's esophagus [7]. Recently, photon-tissue interaction modeling was incorporated into an optical study of murine tumors consisting of human pancreatic cancer cells, in order to quantitatively distinguish different tumor regions [8]. Z. Volynskaya, et al., “Diagnosing breast cancer using diffuse reflectance and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008); G. Zonios, et al., “Diffuse reflectance spectroscopy of adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628-6637 (1999); S. K. Chang, et al., “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt. 11, 024008 (2006); I. Georgakoudi and M. S. Feld, “The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett's esophagus,” Gastroint. Endosc. Clin. N. Am. 14, 519-537 (2004); and V. Krishnaswamy, et al., “Quantitative imaging of scattering changes associated with epithelial proliferation, necrosis, and fibrosis in tumors using microsampling reflectance spectroscopy,” J. Biomed. Opt. 14, 014004 (2009).